基于无线双极电极的电致化学发光生物分析系统研究

The development of simple and sensitive miniaturized electrochemiluminescence (ECL) biosensor has attracted particular interest of scientists. Wireless ECL biosensor based on bipolar electrode is one of the hot advance research of miniaturized ECL biosensor. Compared with the tradditional three-electrode ECL biosensor, wireless ECL biosensor offers some remarkable advantages, such as low sample consumption, short assay time, portable and rich imformation obtanined. This project is based on our previous studies which used bipolar electrode based ECL strategy for sensitive determination of cancer biomarkers and cells.Here, we carries out some innovative research work as follows: synthesis ECL nanoparticles with excellent biocompatibility and develop novel signal amplifacation techeniques using nanoparticles to improve the sensitivity of wireless ECL biosensor; synthesis and select bipolar electrode materials with excellent conductivity and transparency to improve the ECL performance on bipolar electrode; prepare multifunctional biosensor array to realize multiplexed detection in complex matrix; investigate and develop microfluidic biosensor for visual detection which integrates sample preparation, reaction, and multiplexed detection; then establish the calibration graphs and fabricate direct-reading visual biosensor array; furthermore, design and fabricate multi-channel visual microfluidic biosensor arrays with various functions, such as enrichment of biomolecules and cells, manipulation, and on-line monitoring. This research develops some simple, sensitive, portable, and visual biosensor arrays which could realize multiplexed bioanalysis and the early diagnosis of diseases. It provides an effective method for life science research.

简单便携、高灵敏的微型化电致化学发光(ECL)生物传感器的发展一直以来深受关注，而基于双极电极的无线ECL生物传感器是其中的前沿研究方向之一。本项目以我们前期所建立的无线电致化学发光技术实现高灵敏的肿瘤标志物和细胞的检测为基础，具体研究内容包括：研究并制备生物相容性好的ECL纳米材料，开发高效的信号放大技术；合成并筛选导电性和透光性良好的电极材料；研制多功能传感器阵列，进一步研发集采样、反应和多组分同时检测为一体的微型可视化传感器，并在此基础上建立标准图谱，制备直读型可视化检测传感器阵列；构建多通道微流控芯片，研制具有不同功能的可视化传感器阵列芯片，如：生物分子和细胞的富集、操纵、在线监测等，提高单个分析流程中获取信息的深度和广度，使之能广泛地用于多种生物分子的同时识别和检测，实现疾病的早期诊断，为生命科学研究提供有用、简便的测试方法。

本项目在构建简单、便携的电致化学发光生物传感器件方面开展了一系列的工作。由于双极电极的电致化学发光技术主要采用单根双极电极、而且由于电极尺寸较小，对其表面进行特异性修饰存在一定的困难，此外，在可视化分析方面的应用非常少。本项目主要进行了以下几方面的研究：1、考察了开放式双极电极体系和闭合式双极电极体系在电致化学发光方面的差异性，并进行了机理研究；2、构建了多通道双极电极阵列，并在其一端进行选择性修饰和生物分子的组装，成功的构建了双极电极可视化传感器阵列芯片，并用于多种肿瘤标志物的同时捕获和检测；3、对双极电极一端进行改性，构建了杂化双极电极，并考察其对双极电极界面电化学反应的影响；4、成功的制备了电化学纳米颗粒，并对双极电极界面电致化学发光信号进行调控；5、构建了双信号识别系统，用于肿瘤细胞的高特异性识别和检测。实现了多根电极同时电致化学发光分析，可视化芯片的研究以及高效信号放大技术的研究。成功的在一块芯片上构建了多种生物传感单单元，实现了多组分同时成像分析。本研究极大提高了检测的速度和灵敏度，为构建简便、高灵敏、高通量生物分析提供新型检测平台。